US 11,981,744 B2
Chimeric polypeptide assembly and methods of making and using the same
Volker Schellenberger, Palo Alto, CA (US); Fan Yang, San Jose, CA (US); Desiree Thayer, Burlingame, CA (US); Bee-Cheng Sim, Mountain View, CA (US); and Chia-Wei Wang, Santa Clara, CA (US)
Assigned to AMUNIX PHARMACEUTICALS, INC., Mountain View, CA (US)
Filed by AMUNIX PHARMACEUTICALS, INC., Mountain View, CA (US)
Filed on Dec. 19, 2022, as Appl. No. 18/067,948.
Application 18/067,948 is a division of application No. 15/753,716, granted, now 11,713,358, previously published as PCT/US2016/049137, filed on Aug. 26, 2016.
Claims priority of provisional application 62/379,673, filed on NaN, NaN.
Claims priority of provisional application 62/363,046, filed on Jul. 15, 2016.
Claims priority of provisional application 62/338,285, filed on May 18, 2016.
Claims priority of provisional application 62/278,755, filed on Jan. 14, 2016.
Claims priority of provisional application 62/263,319, filed on Dec. 4, 2015.
Claims priority of provisional application 62/211,532, filed on Aug. 28, 2015.
Prior Publication US 2023/0295334 A1, Sep. 21, 2023
Int. Cl. C07K 16/30 (2006.01); A61P 35/00 (2006.01); C07K 14/00 (2006.01); C07K 16/28 (2006.01); C12N 5/09 (2010.01); A61K 38/00 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/30 (2013.01) [A61P 35/00 (2018.01); C07K 14/00 (2013.01); C07K 16/2809 (2013.01); C12N 5/0693 (2013.01); A61K 38/00 (2013.01); A61K 2039/505 (2013.01); A61K 2039/54 (2013.01); A61K 2039/545 (2013.01); A61K 2039/572 (2013.01); C07K 2317/24 (2013.01); C07K 2317/31 (2013.01); C07K 2317/55 (2013.01); C07K 2317/56 (2013.01); C07K 2317/565 (2013.01); C07K 2317/60 (2013.01); C07K 2317/622 (2013.01); C07K 2317/73 (2013.01); C07K 2317/732 (2013.01); C07K 2317/76 (2013.01); C07K 2317/90 (2013.01); C07K 2317/92 (2013.01); C07K 2317/94 (2013.01); C07K 2319/01 (2013.01); C07K 2319/035 (2013.01); C07K 2319/21 (2013.01); C07K 2319/30 (2013.01); C07K 2319/31 (2013.01); C07K 2319/50 (2013.01); C12N 2523/00 (2013.01)] 10 Claims
 
1. A method of treating prostate cancer in a subject in need thereof, comprising intravenously administering to the subject a therapeutically effective amount of a chimeric polypeptide assembly,
wherein the chimeric polypeptide assembly comprises a bispecific antibody comprising
i. a first antibody binding domain having binding specificity to PSMA, wherein the first antibody binding domain is a Fab, and
ii. a second antibody binding domain having binding specificity to CD3, wherein the second binding domain comprises an scFv,
wherein the second antibody binding domain is attached to a bulking moiety via a linker comprising a peptidyl release segment that is capable of being cleaved by at least one mammalian protease, and wherein the bulking moiety (i) reduces the ability of the second antibody binding domain to bind CD3 and (ii) comprises an albumin binding domain;
wherein cleavage of the peptidyl release segment by the at least one mammalian protease converts the chimeric polypeptide assembly into an activated bispecific antibody,
wherein the activated bispecific antibody is capable of effecting at least a 10-fold greater amount of cell lysis of tumor cells compared to the chimeric polypeptide assembly, when cell lysis is measured in an in vitro assay comprising the tumor cells and a population of human peripheral blood mononuclear cells (PBMCs) comprising T cells.